Today more than 80000 allogeneic bone marrow
transplantations (BMT) have been performed worldwide. The major indications are
hematological malignancies such as
acute myeloid leukemia (AML),
acute lymphoblastic leukemia (ALL),
chronic myeloid leukemia (CML) and
myelodysplastic syndromes. Unrelated donors are increasingly used and there are around 4 million volunteer donors available in different registers, the largest being the National Marrow Donor Program. Molecular typing has improved the typing technique which has resulted in a decreased risk of
graft-versus-host disease (GVHD), lower transplant-related mortality (TRM) and improved
leukemia-free survival (LFS). Using HLA-identical siblings, patients with AML in first complete remission (1 CR) and high-risk ALL in 1 CR are clear indications for BMT. However, if an HLA-identical sibling is not available, it is not known today if an unrelated bone marrow or
autografting is the best option for all patients with acute
leukemia in 1 CR. Because BMT is the only curable treatment for CML, a search for an unrelated donor should start as soon as it is evident that an HLA-identical sibling is not available. BMT within a year from diagnosis is of major importance for outcome. Allogeneic peripheral blood progenitor cells (PBPC) have been used as an alternative to bone marrow. Preliminary studies indicate a faster engraftment, but prospective randomized trials are necessary to establish the role of allogeneic PBPC. Umbilical cord blood has also been used as a source of allogeneic hematopoietic stem cells. Using cord blood from HLA-identical siblings, engraftment seems to be delayed, but the probability of GVHD is low. Preliminary data using unrelated cord blood cells are encouraging. GVHD has an important antileukemic effect. Recently, a graft-versus-myeloma and a graft-versus-
breast-cancer effect has been demonstrated. In patients who relapse after BMT, donor lymphocytes can induce remission, especially in patients with CML. With molecular techniques it is possible to detect relapse at an early stage, so called
minimal residual disease.
Liposomal amphotericin B has few side-effects and decreased the death rate by
invasive fungal infection in BMT recipients. Early diagnosis and treatment of cytomegalovirus (CMV)
infection with new
antiviral drugs have dramatically reduced the incidence and mortality in CMV disease.
Cyclosporine combined with
methotrexate is today the most widely used immunosuppressive regimen and has decreased GVHD and improved survival. However, several new immunosuppressive drugs need to be explored in clinical BMT. Immune modulation by for instance
cytokines and
cytokine inhibititors is a new exciting development.